The specific aims of this proposal test the hypothesis that retinal ganglion cells and their axons survive optic nerve transection and have the intrinsic potential for regenerative growth. Specific Aim I will involve the quantitative assessment of the number and diameter of surviving optic axons at various times after intracranial nerve transection. This will be accomplished by a computer controlled system which automatically samples material on the electron microscopic level. The investigation will be carried out in both adult and neonatal mice. Specific Aim II will examine the number, size, and retinal location of cells in the ganglion cell layer which survive optic nerve transection. This will be accomplished by the semi-automated counting of Nissl-stained retinal whole mounts as well as by qualitative investigations using retrograde tracing techniques involving horseradish-peroxidase (HRP). Specific Aim III will test the effects of prosthetic bridging devices applied to the transected optic nerve in terms of the number of axons and retinal ganglion cells that survive. These experiments will involve implanting sciatic nerve grafts and biodegradable 'nerve guides', as well as the direct application of substances to the severed nerve via a 3-dimensional collagen matrix inside the 'nerve guide'. The long-term objectives of this research program to develop a model of regenerative growth in the mammalian central nervous system which can easily test the effects of various experimental manipulations (e.g. pharmacologic agents and neural prostheses) using automated quantitative techniques. The results of this three year project will provide standard quantitative data concerning the survival of optic axons and ganglion cells, and their regenerative potential, following nerve transection. Such information should be useful to many laboratories interested in CNS regeneration, as well as clinicians and basic scientists working with the visual system.